title: Specific targeting of HER2 overexpressing breast cancer cells with doxorubicin-loaded trastuzumab-modified human serum albumin nanoparticles.
abstract: Specific targeting of tumor cells to achieve higher drug levels in tumor tissue and to overcome cardiotoxic and other secondary effects is the major goal in cancer therapy. With trastuzumab as a humanized monoclonal antibody binding, the HER2 receptor specific targeting is possible. In the present study, target-oriented nanoparticles based on biodegradable human serum albumin (HSA) loaded with cytostatic drug doxorubicin were developed. The surface of the nanoparticles was modified by covalent attachment of trastuzumab. HER2 overexpressing breast cancer cells showed a good cellular binding and uptake of these nanoparticles. The specific transport of the cytostatic drug doxorubicin with this nanoparticulate formulation into the HER2 overexpressing breast cancer cells, their release, and biological activity was demonstrated. The results indicate that these cell-type specific drug-loaded nanoparticles could achieve an improvement in cancer therapy. To our knowledge, this is the first study demonstrating a specific trastuzumab-based targeting of HER2 overexpressing breast cancer cells with doxorubicin-loaded nanoparticles.
authors.affiliation: Institute of Pharmaceutical Technology, Biocenter of Johann Wolfgang Goethe-University, 60438 Frankfurt/Main, Germany.
authors.forename: Marion G
authors.initials: MG
authors.lastname: Anhorn
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wagner
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
authors.forename: Klaus
authors.initials: K
authors.lastname: Langer
authors.forename: Hagen
authors.initials: H
authors.lastname: von Briesen
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D054697:Cytostatic Agents / Q000378:metabolism / Q000494:pharmacology; D004317:Doxorubicin / Q000378:metabolism* / Q000494:pharmacology; D004337:Drug Carriers / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D053758:Nanoparticles; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012709:Serum Albumin; D013379:Substrate Specificity; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D054697:Cytostatic Agents; D004317:Doxorubicin; D004337:Drug Carriers; D018719:Erb-b2 Receptor Tyrosine Kinases; D012709:Serum Albumin; D000068878:Trastuzumab